OBJECTIVE: To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2). METHODS: Three children who were diagnosed with ILFS2 at the Children's Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). RESULTS: The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c.3596G>A and c.1181A>T in child 1, c.2617C>T and c.2T>C in child 2, and c.3596G>A and c.2817_2818insT in child 3. Among these, the c.1181A>T and c.2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+PM3+PP3) and pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION Combined with the patient's clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.
Humans ; Exome Sequencing ; Genetic Testing/methods* ; Liver Failure, Acute/etiology* ; Mutation ; Child ; Adult ; Neoplasm Proteins

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

Objective:To discuss the effect of urolithin C(UC)on the proliferation,apoptosis,and autophagy of the acute myeloid leukemia(AML)HL-60 cells,and to clarify its mechanism.Methods:The HL-60 cells were divided into different concentrations(20,40,60,80,and 100 μmol·L-1)of urolithin A(UA)groups,urolithin B(UB)groups,and UC groups.CCK-8 assay was used to detect the proliferation activity of the cells in various groups;the morphology of the cells in different concentrations of UC groups was observed under optical microscope.The HL-60 cells were divided into different concentrations(0,20,40,and 80 μmol·L-1)of UC groups and 3-methyladenine(3-MA)combined with different concentrations(0,20,40,and 80 μmol·L-1)of UC groups.CCK-8 assay was used to detect the proliferation activities of the cells in various groups.The HL-60 cells were divided into control group(0 μmol·L-1)and different concentrations(20,40,and 80 μmol·L-1)of UC groups.The live/dead cell staining method was used to detect the dead rates of the cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups;the autophagy of the cells was detected by autophagy staining kit(monodansylcadaverine,MDC)method;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Beclin 1,autophagy related gene 9(ATG9),and autophagy related gene 7(ATG7)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of cysteinyl aspartate specific proteinase-3(Caspase-3),cleaved cysteinyl aspartate specific proteinase-3(Cleaved Caspase-3),microtubule-associated protein 1 light 3(LC-3),extracellular regulated protein kinases(ERK),phosphorylated ERK(p-ERK),AMP-activated protein kinase(AMPK),and phosphorylated AMPK(p-AMPK)in the cells in various groups.Results:The CCK-8 assay results showed that after cultured for 24,48,and 72 h,compared with 0 μmol·L-1 UA,UB,and UC groups,the proliferation activities of the cells in different concentrations of UA,UB,and UC groups were decreased(P＜0.01)with a concentration-and time-dependent manner;at 48 h,compared with UA and UB,the half-maximal inhibitory concentration(IC50)of UC was the lowest.The cell morphology observation results showed that compared with control group,the intercellular connection and the number of the cells were decreased with the increasing of UC concentration,and the cell fragment was increased.The CCK-8 assay results showed that compared with 40 and 80 μmol·L-1 UC groups,the proliferation activities of the cells in 3-MA combined with 40 and 80 μmol·L-1 UC groups were increased(P＜0.05 or P＜0.01).The live/dead cell staining results showed that compared with control group,the dead rates of the cells in 40 and 80 μmol·L-1 UC groups were increased(P＜0.01).The flow cytometry results showed that compared with control group,the apoptotic rate of the cells in 80 μmol·L-1 UC group was increased(P＜0.01).The MDC method results showed that with the increasing of UC concentration,the green fluorescence in the cells in different concentrations of UC groups was gradually intensified.The RT-qPCR results showed that compared with control group,the expression levels of Beclin 1,ATG9,and ATG7 mRNA in the cells in 80 μmol·L-1 UC group were increased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of Cleaved Caspase-3 protein in the cells in 20,40,and 80 μmol·L-1 UC groups were increased(P＜0.01),the ratio of membrane LC3/cytoplasmic LC3(LC3-Ⅱ/LC3-Ⅰ)in the cells in 80 μmol·L-1 UC group was increased(P＜0.05),and the ratios of p-AMPK/AMPK and p-ERK/ERK in the cells in 40 and 80 μmol·L-1 UC groups were increased(P＜0.01).Conclusion:UC can inhibit the proliferation of the AML HL-60 cells,induce the apoptosis and autophagy,and increase the phosphorylation levels of ERK and AMPK proteins in the cells.

Objective To study the effects and mechanism of norcantharidin(NCTD)on proliferation and apoptosis of NB4 and K562 human leukemic cells by regulating phosphoprotein phosphatase 5 catalytic(PPP5C).Methods PC3.1 and PPP5C-PC3.1 plasmids were electroporated into NB4 and K562 cells.Stable NB4 and K562 cell lines were selected with geneticin(G418).Protein and mRNA expression levels of PPP5C were measured by Western blot and RT-qPCR,respectively.Proliferation,migration,and apoptosis of NB4 and K562 cells were determined by a CCK-8 assay,transwell assay,and Live & Dead? animal cell viability/toxicity detection kit,respectively.NB4 and K562 cells were divided into 0 μg/mL NCTD group and various NCTD dose groups,and cultured in RPMI 1640 medium containing 0,8,16,or 32 μg/ml NCTD.The Live & Dead? animal cell viability/toxicity detection kit measured the numbers of dead and live cells,and cell morphology was observed under a microscope.Western blot was used to measure protein expression levels of caspase 3,Cleaved caspase 3,JNK,p-JNK,p38,p-p38,and α-Tubulin.Results Proliferation,migration,and apoptosis of NB4 and K562 cells were enhanced by overexpression of PPP5C.Compared with 0 μg/mL NCTD group,NCTD promoted apoptosis in a dose-dependent manner.PPP5C overexpression antagonized the killing effect of NCTD on leukemic cells.Mechanistic investigations showed that PPP5C reduced the protein level of p-JNK by dephosphorylating and regulating the expression of apoptosis-related protein Cleaved caspase 3.Conclusions NCTD promotes apoptosis of NB4 and K562 cells and inhibits their proliferation by inhibiting PPP5C.

Objective:To estimate tissue/organ doses and effective dose to operators in the overexposure incident during an interventional procedure using Monte Carlo method.Methods:The phantoms were constructed for both the operators and the patient based on the adult mesh-type reference computational phantoms (MRCPs) recommended by the International Commission on Radiological Protection (ICRP) Publication 145 and phantom deformation technology. Models of exposure scenario were constructed based on the on-site equipment and the irradiation conditions. The Monte Carlod simulation method was used to evaluate the absorbed dose to critical tissues and organs, such as the operator′s eye lens and thyroid, as well as the effective dose.Results:In the particular exposure conditions, the maximum absorbed doses in the primary organs of the two operators were in the left eye lens, with doses of 1.216 and 0.223 mGy, respectively. The thyroid absorbed doses were 0.074 and 0.019 mGy, while the effective doses to the two operators were 0.088 and 0.021 mSv, respectively. The reduction rates of effective dose for the two operators when wearing lead aprons and lead thyroid collars were 67.16% and 78.79%, respectively.Conclusions:The combination of Monte Carlo method and MRCPs can be used to restore a specific irradiation scenario to a high degree and to estimate the physical dose of to the irradiated persons.

OBJECTIVE To evaluate the post-marketing safety of Compound porcine cerebroside and ganglioside injection in patients with ischemic stroke. METHODS A drug-induced， prospective， non-controlled clinical study design was conducted. Using the patients with ischemic stroke who received Compound porcine cerebroside and ganglioside injection at least once in 46 secondary class A and above medical institutions across the country from April 2020 to May 2021 as the monitoring objects， and their basic data， medication information and the occurrence of adverse drug reactions were analyzed. RESULTS Among 13 514 patients with ischemic stroke， the incidence of adverse events was 10.01%， and the incidence of adverse reactions related to Compound porcine cerebroside and ganglioside injection was 0.33%. Drug-related adverse drug reactions were mild or moderate， concentrated in the gastrointestinal system （18 cases）， skin and subcutaneous tissue （10 cases）， nervous system （7 cases） and other systems/organs， mainly including constipation， abdominal pain， diarrhea， rash， pruritus， dizziness and other symptoms. Most of the patients （91.03%） recovered or improved after treatment， and 2 patients died. Among the 45 patients with adverse drug reactions， 84.44% were cured or improved after drug withdrawal or symptomatic treatment， and 15.56% had no significant change. The incidence of adverse drug reactions in tertiary hospitals was significantly higher than that in secondary hospitals， and the incidence of adverse drug reactions in patients with allergic history was significantly higher than that in patients without allergic history （P＜0.05）. Irrational drug use was found in 2.76% of patients， and the incidence of adverse drug reactions（2.95%） was significantly higher than that in patients without irrational drug use（0.26%，P＜0.05）. CONCLUSIONS The adverse drug reaction symptoms of ischemic stroke patients treated with Compound porcine cerebroside and ganglioside injection are relatively common， the incidence rate is generally low， and it is related to the patients’ physique and whether the drug use is standardized.

Objective:To investigate the expression of nicotinamide-N-methyltransferase (NNMT) in various tumor tissues and its prognostic value in papillary thyroid carcinoma.Methods:The paraffin samples of surgically resected tissues from 168 cases of colorectal cancer, 75 cases of gastric cancer, 178 cases of lung cancer, 15 cases of liver cancer, 60 cases of thyroid cancer, 7 cases of prostate cancer, 74 cases of breast cancer, and 14 cases of renal cancer were collected from Sir Run Run Show Hospital, Zhejiang University School of Medicine and the Third Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine between January 2016 and December 2021; tissue samples of 58 cases of papillary thyroid cancer and another 19 cases of thyroiditis were collected between January 2016 and December 2016. Immunohistochemistry kits were prepared and performance tests were performed. Normal specimens (>5 cm from the margin of paracancerous tissues) and the samples of gastric cancer, colorectal cancer, lung cancer, thyroid cancer, prostate cancer, breast cancer, and kidney cancer tissues as well as their paracancerous tissues (3 cm from the tumor edge) were selected. Immunohistochemistry kits were used to detect the expression of NNMT protein in normal tissue samples, different tumor tissues and their paracancerous tissues. X-tile software combined with the receiver operating characteristics curve of NNMT in the diagnosis of tumor tissues and paracancerous tissues in papillary throid carcinoma were used to determine the optimal cut-off value (41.5); < 41.5 was treated as the NNMT protein low expression group and ≥ 41.5 was treated as the NNMT protein high expression group. The expression of NNMT protein in patients with papillary thyroid carcinoma with different clinicopathological characteristics was compared; Kaplan-Meier method was used to analyze the overall survival of the patients with papillary thyroid carcinoma; Cox proportional risk model was used to conduct multivariate analysis on the influencing factors of overall survival.Results:The prepared immunohistochemistry kits were valid for at least 12 months, with good intra-batch and batch-to-batch repeatability, good stability and specificity. NNMT protein was not or occasionally lowly expressed in colorectal, lung, thyroid, prostate, breast, kidney, and gastric tissues. NNMT protein was highly expressed in colorectal cancer, gastric cancer, breast cancer, kidney cancer, thyroid cancer, lung cancer, prostate cancer tissues, while lowly expressed in colorectal cancer, gastric cancer, breast cancer, kidney cancer, thyroid cancer, lung cancer, prostate cancer adjacent tissues. The high expression rates of NNMT protein in thyroiditis tissue, papillary thyroid cancer tumor tissue and paracancerous tissues were 15.79% (3/19), 68.97% (40/58) and 31.03% (18/58), respectively, and the high expression rate of NNMT protein in papillary thyroid carcinoma tissue was higher than that in thyroiditis tissue and paracancerous tissue. All patients with papillary thyroid cancer were divided into the NNMT protein high expression group (40 cases) and the low expression group (18 cases). There were no statistically significant differences in NNMT protein expression among patients with different age, gender, degree of differentiation, lump diameter, TNM stage, lymph node metastasis, and serum anti-thyroglobulin antibody (TgAb) level (all P > 0.05). The median overall survival time of 58 patients was 18.5 months, and the 5-year overall survival rate was 90.0%. The overall survival of patients with a lump diameter of ≥2 cm was worse than that of those with a lump diameter of < 2 cm ( P < 0.001), and the overall survival of patients with lymph node metastasis was worse than that of those without lymph node metastasis ( P = 0.041). The overall survival of patients in the NNMT protein high expression group was worse than that of those in the NNMT protein low expression group, and the overall survival of patients with high serum TgAb level was worse than that of those with low serum TgAb level, while the differences were not statistically significant (all P >0.05). Lump diameter ( HR = 35.56, 95% CI 2.64-478.25, P = 0.007), NNMT protein expression ( HR = 308.12, 95% CI 2.21-42 958.20, P = 0.023), serum TgAb level ( HR = 142.85, 95% CI 1.88-10 854.25, P = 0.025) were independent influencing factors for the OS of patients with papillary thyroid carcinoma. Conclusions:NNMT is highly expressed in various tumor tissues. NNMT expression is related to the prognosis of patients with papillary thyroid carcinoma;the patients with high expression of NNMT have worse prognosis compared with those with low expression of NNMT.

Objective To explore the prognostic factors of primary mediastinal large B-cell lymphoma (PMBCL) and the effects of chemoradiotherapy versus chemotherapy alone on patients' prognosis before and after rituximab era. Methods We extracted the data of PMBCL patients diagnosed from 2001 to 2015 from SEER database. SEER Stat software was used to calculate the incidence rate. Kaplan-Meier method and Cox regression model were used to analyze the impact of various clinical variables on prognosis. Results We included 635 patients with PMBCL. Multivariate Cox regression analysis showed that age, stage and chemotherapy were independent prognostic factors. Kaplan-Meier survival analysis showed that OS of the patients receiving chemotherapy only in 2006-2015 was significantly better than that in 2001-2005 (χ²=10.002, P=0.002). The patients who received chemoradiotherapy had better OS than those who received chemotherapy alone from 2001 to 2005. The OS and DSS of patients receiving chemoradiotherapy were not significantly different from those of chemotherapy alone from 2006 to 2015. Conclusion The application of rituximab improves the long-term survival of PMBCL patients. The prognosis of patients who received chemoradiotherapy is comparable to that of chemotherapy alone from 2006 to 2015.

Objective: To carry out the 4^th round of third-party evaluation on the implementation and effect of the 1^st year of the 2^nd Phase National Healthcare Improvement Initiative(abbreviated as Initiative)since 2015. Methods: The 4^th round of the evaluation survey adopted the same methods, organization and execution, and technical roadmap as the former three rounds of evaluations. Results: The 4^th round of evaluation was carried out from 18 March to 9 April, 2019 at 185 public hospitals in 31 provinces(autonomous regions, municipalities directly under the Central Government)and Xinjiang Production and Construction Corps.Facility survey, health professional survey and patient survey were conducted at each of the sample health facilities. A total of 120 782 valid questionnaires were collected from 144 non-psychiatric health facilities, 16 246 valid questionnaires were obtained from 41 psychiatric health facilities, and 252 cases of outstanding departments/hospitals in healthcare improvement were also collected. The average overall scoring of the 12 dimensions to assess Initiative implementation at 144 non-psychiatric health facilities was 84.4%. The overall outpatient satisfaction scoring was 91.1%, 96.7%for the inpatients. The overall inpatient satisfaction(family members inclusive) at 41 psychiatric health facilities was 93%. Areas remaining to be improved include day-surgery, telemedicine and medical social work. Compared with technical services, non-technical care should be further strengthened. The compensation, workload and work environment of the healthcare providers are still to be improved. Conclusions The implementation of the Initiative by health facilities has been greatly improved. The percentage of health facilities and patients who had positive perceptions of improved doctor-patient relationship has been increasing. Patient care experiences at public hospitals have been generally improved, and the implementation of promoting traditional Chinese Medicine practices also made progress. However, work satisfaction of healthcare providers was found to be rather low, compared to the high level of patient satisfaction.

Objective:To explore the characteristics of cognitive function in patients with early onset and adult onset schizophrenia.Methods:In this cross-sectional study, 546 patients with schizophrenia who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) were selected.Among them, 62 cases were defined as early onset schizophrenia (EOS, age of onset＜18 years) and 175 patients were defined as adult onset schizophrenia (AOS, age of onset≥25 years).Patients underwent clinical assessments with the Positive and Negative Symptom Scale (PANSS) and the Personal and Social Performance Scale (PSP), and comprehensive neuropsychological assessments.Results:The EOS patients got lower scores in motor function-PEGDOM T score [ (26±12) vs. (30±11), P＜0.01], working memory-average T score of PASAT and WMSSP[ (34±12) vs. (38±10), P＜0.05]and executive function (inhibition) -Stroop T score [ (35±12) vs. (39±10), P＜0.05]than AOS patients.No differences were fund in processing speed, verbal memory and learning, visual memory and learning (Ps＞0.05) between the two groups.Conclusion:It suggests that the EOS patients have worse motor function, working memory and inhibition.